Carbonyl compounds reduction, asymmetric induction

The prime functional group for constructing C-C bonds may be the carbonyl group, functioning as either an electrophile (Eq. 1) or via its enolate derivative as a nucleophile (Eqs. 2 and 3). The objective of this chapter is to survey the issue of asymmetric inductions involving the reaction between enolates derived from carbonyl compounds and alkyl halide electrophiles. The addition of a nucleophile toward a carbonyl group, especially in the catalytic manner, is presented as well. Asymmetric aldol reactions and the related allylation reactions (Eq. 3) are the topics of Chapter 3. Reduction of carbonyl groups is discussed in Chapter 4. 

In 1972, Tsuchihashi disclosed that the carbanion (28 Ar = p-tolyl), generated from (/ )-methyl p-tolyl sulfoxide with lithium diethylamide, adds to benzaldehyde or a-tetialone to give an adduct (29) in a dia-stereomeric ratio of 50 50 or 64 36, respectively. Additions of this carbanion to various unsymmetrical ketones are also reported to be poorly diastereoselective (for example, EtCOMe 50 50, Bu COMe 55 45, Bu COPh 70 30). Note that in the case of Ar = 2-pyridyl a chiral sulfinyl group increases the asymmetric induction observed in the addition of the corresponding carbanion to carbonyl compounds (PhCHO 80 20, R-C9H19CHO 70 30). Since diastereomer pairs of (29) are separable, chromatographic separation followed by reductive desulfurization with Raney Ni provides a method for obtaining optically active alcohols (30 Scheme 9). 

In addition to asymmetric hydroboration of C=C, the hydroborating reagents also exhibit remarkable asymmetric induction in the reduction of the carbonyl moiety. Chiral organoboranes derived via hydroboration with 9-BBN are proven to be highly useful for the asymmetric reduction. The characteristics of asymmetric induction in the reduction of prochicral carbonyl compounds of individual chiral organoboranes are discussed in this chapter. 

Brown and Pai have reported [3] that the dissociation problem is also overcome by carrying out the reaction with the Alpine-Borane either as neat reagent or concentrated solutions (>2 M). The reduction of a wide range of prochiral carbonyl compounds with good to excellent asymmetric induction has been achieved. The reduction is performed at 25 °C by using either a 100 or 40% excess (for reactive substrate) of the reagent, synthesized by the hydroboration of commercial available 92% ee (-t)-a-pinene with 9-BBN. On completion of the... 

S. Colonna and R. Fornasier. Asymmetric induction in the borohydride reduction of carbonyl compounds by means of chiral phase-transfer catalysts. Part 2. J.C.S. Perkin 1,1978, 371. 

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